Clinical evaluation of a topical Unani pharmacopoeial formulation Tila-e-Kalf in the management of melasma (Kalf): A randomized controlled clinical trial.

Objective: Melasma is a chronic, acquired, symmetrical hyper melanosis of skin, characterized by irregular light to dark brown patches on sun-exposed areas, with a significant effect on psychological health; melasma is termed as Kalf in Unani medicine. Conventional treatments have transitory results and often carry adverse effects like skin irritation, scarring, etc. This study was planned to evaluate the safety and efficacy of a Unani pharmacopoeial formulation Tila-e-Kalf, comprising of lentil (Lens culinaris), bitter almond (Prunus amygdalus), and fig (Ficus carica), and to compare its efficacy with standard drug hydroquinone in patients of melasma. Materials and Methods: This was an 8-week open-label, standard controlled, randomized clinical study conducted on patients of epidermal melasma. The test group received Tila-e-Kalf while the control group received hydroquinone 4% cream for local application once daily. Efficacy was assessed by MASI (Melasma Area Severity Index), DLQI (Dermatology Life Quality Index), and PGA (Physician Global Assessment) and colored photographs. Results: Mean MASI score decreased from10.65±0.85 to 7.07±0.74 in the test group (p<0.0001) and from 11.28±1.24 to 7.76±0.9 (p<0.0001) the in control group. Similar improvement was noticed in other parameters also. A large number of patients in the control group reported mild burning, itching, dryness, and skin rashes, while only one patient in the test group reported mild itching. Conclusion: Tila-e-Kalf as a topical depigmenting agent was found equally effective with better tolerability and safety as compared to hydroquinone.

A Polyherbal Formulation Habb-e-Ustukhuddus Induces Apoptosis and Inhibits Cell Migration in Lung and Breast Cancer Cells without Any Toxicity in Mice.

OBJECTIVE: A polyherbal medicine, Habb-e-Ustukhuddus (HU), is used for its anti-inflammatory properties. However, the anticancer and chemopreventive properties of HU were not known, and Therefore, investigated in  the  present study. METHODS: Cancer cells were treated with 50-400 µg/ml HU and MTT, trypan blue, and clonogenic assays were performed. Propidium iodide (PI) staining, annexin V-FITC assay, and JC-1 staining were done for cell cycle progression, apoptosis, and mitochondrial membrane potential, respectively, using flow cytometry. Immunoblotting, cell migration and invasion assays were performed. Chemical characterization of HU was done through GC-MS and HPLC analyses. C57BL/6 mice were used to assess the in vivo toxicity of HU. RESULTS: While evaluating the anticancer activity, the methanolic extract of HU (50-400 µg/ml) strongly inhibited the growth and survival (P<0.05-0.001) of lung and breast cancer cells and increased the cell population in the sub-G1 phase of the cell cycle. HU caused apoptotic death of cancer cells (P<0.05-0.001), which was associated with the depolarization of mitochondrial membrane potential (Δψ) (P<0.001) and an increase in Bax to Bcl-2 protein ratio. Further, HU inhibited the invasion and migration of cancer cells, which was accompanied by an increase in the epithelial marker, E-cadherin, and a decrease in the mesenchymal marker, vimentin. The HU characterization by GC-MS and HPLC analyses showed the abundance of bioactive compounds including flavonoids and alkaloids. In the chemopreventive study, the oral administration of methanolic extract of the formulation HU (50 and 100 mg/kg body weight) to mice did not cause any toxicity and significantly increased the specific activities of hepatic drug metabolizing phase I and phase II enzymes, which suggested for its detoxification potential of xenobiotic compounds. CONCLUSION: Together, these results demonstrated the anticancer potential HU, without any apparent toxicity in mice, and thus HU could be further explored for its clinical utility in cancer control.

Hijamah (Cupping Therapy) for Pain Management in Patients with Cervical Spondylosis.

Background: Cervical spondylosis is the most common cervical spine disorder which is clinically manifested by axial neck pain, stiffness, and limited movement and sometimes it is accompanied by tingling and radicular symptoms in the upper extremities. Pain is the most frequent complaint for which patients, suffering from cervical spondylosis, consult physicians. In conventional medicine, pain and other symptoms of cervical spondylosis are controlled by systemic and local use of non-steroidal anti-inflammatory drugs (NSAIDs), however long-term use of such medicines produces adverse effects like dyspepsia, gastritis, gastroduodenal ulcer and bleeding. Methods: We searched articles for neck pain, cervical spondylosis, cupping therapy, Hijama, etc. from various databases, including PubMed, Google Scholar, and MEDLINE. We also searched for these topics in the books of Unani medicine available in HMS Central Library, Jamia Hamdard, New Delhi, India. Results: This review elucidated that in Unani medicine several non-pharmacological regimens known as Ilaj bi'l Tadbir (Regimenal therapies) are advised in the management of painful musculoskeletal disorders. Hijama (cupping therapy) stands out among all these regimens and in most of the classical Unani literature, Hijama is suggested as one of the best regimens for the management of pain in Waja' al-Mafasil including Waja' al-'Unuq (cervical spondylosis). Conclusion: On going through the classical texts of Unani medicine and published research papers, it may be concluded that Hijama is a safe and effective non-pharmacological treatment for the management of pain due to cervical spondylosis.

Role of AMP-activated protein kinase on cardio-metabolic abnormalities in the development of diabetic cardiomyopathy: A molecular landscape.

Cardiovascular complications associated with diabetes mellitus remains a leading cause of morbidity and mortality across the world. Diabetic cardiomyopathy is a descriptive pathology that in absence of co-morbidities such as hypertension, dyslipidemia initially characterized by cardiac stiffness, myocardial fibrosis, ventricular hypertrophy, and remodeling. These abnormalities further contribute to diastolic dysfunctions followed by systolic dysfunctions and eventually results in clinical heart failure (HF). The clinical outcomes associated with HF are considerably worse in patients with diabetes. The complexity of the pathogenesis and clinical features of diabetic cardiomyopathy raises serious questions in developing a therapeutic strategy to manage cardio-metabolic abnormalities. Despite extensive research in the past decade the compelling approaches to manage and treat diabetic cardiomyopathy are limited. AMP-Activated Protein Kinase (AMPK), a serine-threonine kinase, often referred to as cellular "metabolic master switch". During the development and progression of diabetic cardiomyopathy, a plethora of evidence demonstrate the beneficial role of AMPK on cardio-metabolic abnormalities including altered substrate utilization, impaired cardiac insulin metabolic signaling, mitochondrial dysfunction and oxidative stress, myocardial inflammation, increased accumulation of advanced glycation end-products, impaired cardiac calcium handling, maladaptive activation of the renin-angiotensin-aldosterone system, endoplasmic reticulum stress, myocardial fibrosis, ventricular hypertrophy, cardiac apoptosis, and impaired autophagy. Therefore, in this review, we have summarized the findings from pre-clinical and clinical studies and provided a collective overview of the pathophysiological mechanism and the regulatory role of AMPK on cardio-metabolic abnormalities during the development of diabetic cardiomyopathy.

Cichorium intybus attenuates streptozotocin induced diabetic cardiomyopathy via inhibition of oxidative stress and inflammatory response in rats.

The aim of the present study was to investigate the effects of Cichorium intybus on lipid peroxidation activities of both enzymatic and non-enzymatic antioxidants, inflammatory mediators, myocardial enzymes and histopathology of cardiac tissues in experimental diabetic cardiomyopathy (DCM). DCM was induced by single intraperitoneal injection of streptozotocin (STZ) (40 mg/kg) combined with high energy intake in rats. Seed extract of Cichorium intybus (CIE) (250 mg/kg & 500 mg/kg) was administered orally once a day for 3 weeks. Phytochemical investigations of seed extract revealed presence of some active ingredients such as alkaloids, tannins, saponin, phenols, glycosides, steroids, terpenoids and flavonoids. Seed extract of Cichorium intybus confirmed a significant potency towards restoring the blood glucose, an elevation of the levels of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), superoxide dismutase (SOD), thiobarbituric acid reactive substances (TBARS), blood glutathione (GSH), TNF-α and IL-6 and a reduction in the levels of catalase (CAT) was observed following the STZ treatment. Oxidative stress was accompanied by myocardial degeneration as evidenced by histopathological examination of cardiac tissues. Administration of CIE reduced the lipid peroxides level in heart. Serum levels of AST, GSH, LDH and SOD were brought down to physiological levels by CIE in STZ induced DCM rats. CIE also markedly down-regulated serum TNF-α and IL-6 levels. Catalase that was reduced in serum was brought back to near normal level. The extensive necrotic changes of cardiac tissue by STZ was minimized to normal morphology upon CIE administration. The study demonstrates the cardioprotective effect of CIE via inhibition of oxidative stress and pro-inflammatory cytokines.